Echocardiography in the treatment of
hypertrophic cardiomyopathy
Hipertrofik kardiyomiyopati tedavisinde ekokardiyografi
Echocardiography is the best technique to diagnose, evaluate, follow-up and guide the treatment of hypertrophic cardiomyopathy (HCM). Diagnosis of HCM depends on left ventricular wall thickness ≥15 mm. Also noted are mitral valve systolic anterior motion, an-teriorly positioned mitral valve leaflet coaptation, anomalous anterior insertion of papillary muscles, and diastolic dysfunction. Resting left ventricular outflow tract (LVOT) gradient occurs in 25% of patients and provocable gradients may be demonstrated in more than half of patients. Echocardiography is important for sudden death risk assessment; patients with a wall thickness more than 30 mm ha-ve a higher risk of sudden cardiac death, as often as 2%/year. Two thirds of the symptomatic obstructed patients can be successfully managed long term with medical treatment alone (beta-blockers, disopyramide, verapamil) guided by transthoracic echocardiography (TTE) response and follow-up. Obstructed patients, who fail medical therapy, are usually offered invasive treatment: surgical septal myectomy, alcohol septal ablation, or DDD pacemaker. Preoperative TTE is a necessary guide for the surgeon in planning the opera-tion. It gives the surgeon precise measurements of septal thickness, mitral valve leaflets length and floppiness and papillary muscle anomalies. Intraoperative transesophageal echocardiography is a very important tool for evaluating surgical results. Persistent SAM, resting outflow gradient more than 30 mm Hg or more than 50 mmHg with provocation, moderate to severe mitral regurgitation are in-dications for immediate revision. For patients > 40 years old, and also not suitable for surgery because of comorbidities, alcohol sep-tal ablation is viable alternative therapy for relief of obstruction and improvement of symptoms. Echocardiography is a valuable tool to choose the site of ablation (using myocardial contrast echocardiography), as well as for evaluation of results. (Anadolu Kardiyol Derg 2006; 6 Suppl 2: 18-26)
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Keeyy wwoorrddss:: Hypertrophic cardiomyopathy, obstructive HCM treatment, disopyramide, septal myectomy, alcohol septal ablation, echo-cardiography
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BSTRACT
Dan Musat, Mark V. Sherrid
Hypertrophic Cardiomyopathy Program and Echocardiography Laboratory, Division of Cardiology,
St. Luke's-Roosevelt Hospital Center, Columbia University, College of Physicians and Surgeons, New York City, NY, USA
Hipertrofik kardiyomiyopati (HKM) tan›s›nda, de¤erlendirmesinde, takibinde ve tedavi k›lavuzlu¤unda en iyi teknik ekokardiyografidir. Hipertrofik kardiyomiyopati tan›s› sol ventrikül duvar kal›nl›¤› >=15mm oldu¤unda konulmaktad›r. Bununla birlikte mitral kapa¤›n öne sis-tolik hareketi (SAM), mitral kapakç›klar›n koaptasyonunun anteriyor konumu, papiller adalelerin anormal anteriyor lokalizasyonu ve di-yastolik disfonksiyon görülebilir. ‹stirahat sol ventrikül ç›k›fl gradiyenti (SVÇG) hastalar›n %25 inde ve provokasyonla ortaya ç›kan gra-diyentler hastalar›n >%50 görülmektedir. Ekokardiyografi ani kardiyak ölümün risk de¤erlendirmesi için önemli bir yöntemdir ve 30 mm den fazla duvar kal›nl›¤› olan hastalarda ani ölüm riski daha yüksektir, y›lda %2 prevalans› vard›r. Semptomatik obstrüksiyonu olan has-talar›n 2/3 ekokardiyografi k›lavuzlu¤unda ve takibinde sadece uzun süreli medikal tedavi ile (beta-blokerler, disopiramid, verapamil) baflar›l› olarak takip edilebilirler. Medikal tedaviye cevap vermeyen ve obstrüksiyonu olan hastalara genellikle cerrahi septal miyekto-mi, alkol septal ablasyonu veya DDD pacemaker önerilir. Preoperatif transtorasik ekokardiyografi (TTE), ameliyat› planlayan cerrah için vazgeçilmez bir k›lavuzdur. Ekokardiyografi cerraha septal kal›nl›¤›n›n kesin ölçümlerini, mitral yaprakç›klar›n uzunlu¤unu, sarkmas›n› ve papiller adale anomalilerini gösterir. Cerrahi sonucunun de¤erlendirmesinde intraoperatif transözofajiyal ekokardiyografi çok önem-li bir araçt›r. Acil revizyon için endikasyonlar flunlard›r: persistan SAM, 30 mmHg'dan fazla olan istirahat veya provokasyonla 50 mmHg ç›k›fl yolu gradiyenti ve orta/fliddetli mitral regürjitasyonu. Yafl› 40 tan fazla olan veya komorbiditeler nedeni ile cerrahi için uygun olma-yan hastalarda obstrüksiyonun hafifletilmesi ve semptomlar›n iyileflmesi için alkol septal ablasyonu canl› bir alternatif terapidir. ‹fllemin sonuçlar›n› de¤erlendirmede ve ablasyonun yerini belirlemede (miyokardiyal kontrast ekokardiyografi arac› ile) ekokardiyografi çok de-¤erli bir yöntemdir. (Anadolu Kardiyol Derg 2006; 6 Özel Say› 2: 18-26)
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Annaahhttaarr kkeelliimmeelleerr:: Hipertrofik kardiyomiyopati, obstrüktif HKM tedavisi, disopiramid, septal miyektomi, alkol septal ablasyonu, ekokar-diyografi
Address for Correspondence: Mark V. Sherrid, MD, Professor, Clinical Medicine,
1000 10th Avenue, New York City, NY 10019 USA E-mail: msherrid@chpnet.org
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Role of echocardiography in diagnosis of
hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is clinically defined by a
hypertrophied non-dilated left ventricle in the absence of another
cardiac or systemic disease capable of producing the degree of
left ventricular hypertrophy observed (1). Echocardiography
(ec-ho), widely available, noninvasive, of relatively low cost and with
no contraindications (except sometimes for poor imaging quality)
has proved over the years, to be the best technique to diagnose,
evaluate, follow-up and guide the treatment of HCM (2-5). Most
recent advances towards understanding the pathophysiology,
and developing treatments have employed echo (6,7).
Early echo studies of HCM had used M-mode. A septal to
pos-terior wall thickness ratio of 1.3:1 was considered evidence of
inappropriate septal hypertrophy. With two-dimensional echo the
presence, magnitude, and distribution of left ventricular
hypert-rophy can now be accurately determined. When combined with
co-lor flow and spectral Doppler imaging, echo can fully delineate the
entire spectrum of hemodynamic abnormalities seen in HCM (8).
Currently, HCM is identified by virtue of a maximal left
ventri-cular wall thickness of 15 mm in adult patients or the equivalent
wall thickness relative to body-surface area, in children (1). This
represents an unambiguous and conservative cutoff value. Other
features, useful but not necessary in diagnosing HCM, are: 1)
mit-ral valve systolic anterior motion (absent or mild in nonobstructed
pattern) (9); 2) anteriorly positioned mitral valve leaflet coaptation
(10,11); 3) anomalous anterior insertion of papillary muscles
(12,13), 4) diastolic dysfunction. When a patient is referred for
evaluation and diagnosis of HCM, echo is useful for assessing the
anatomic type, presence of obstruction, and future risk for
sud-den cardiac death.
Echocardiography role in defining types and
assessing obstruction in HCM
Classical HCM is described as asymmetric hypertrophy of the
septum involving the subaortic area of the LV outflow tract.
Besi-des this pattern, HCM can present with hypertrophy in any
seg-ment. According to the degree and distribution of hypertrophy in
left ventricular (LV) short axis views, Gregor et al described 5
types of HCM: 1) type I - hypertrophy affecting only the
intervent-ricular septum; 2) type II - hypertrophy involving besides the
sep-tum, also the left ventricular (LV) anterior or lateral wall; 3) type III
- hypertrophy of the LV posterior wall; 4) type IV - distinct
hypert-rophy of the whole apical LV and septum; and 5) type V -
concent-ric hypertrophy of the LV and septum (14). Type II pattern is the
most frequent (67%) followed by type I (14%), with least
encoun-tered being the type III (4%). Other studies have confirmed that
HCM mainly occurs in one of the three major areas: septum, mid
cavity or apical (15-18). There was no evidence of a
transformati-on from transformati-one form of hypertrophic cardiomyopathy to the other
(15). All three forms could present with or without obstruction,
though obstruction is uncommon in the mid and apical variants.
During the echo evaluation of patients with HCM it is
impor-tant to assess for obstruction, both by evaluating anatomy - i.e.
mitral-septal contact or systolic wall apposition - and by Doppler
(19). Obstruction in HCM is a dynamic phenomenon, depending
on the loading conditions and contractility. Resting left
ventricu-lar outflow tract (LVOT) gradient occurs in 25% of patients but
provocable gradients are more prevalent and obstruction may be
demonstrated in more than half of patients after exercise (20). In
non-obstructive patients it is important to try provocative
mane-uvers to elicit obstruction because obstruction offers a target for
treatment of symptoms. Provocative maneuvers are done during
pulsed or continuous wave Doppler in 5-chamber and 3-chamber
apical views (21), and include: Valsalva's maneuver (22-24),
stan-ding up from a lying down position (22), postprandial (25),
tread-mill exercise (20), amyl nitrite inhalation (20,26). Amyl nitrite and
dobutamine are not physiologic stimuli, which do not mimic
acti-vities of daily life and generally are not recommended. Also,
do-butamine may cause obstruction in normals.
Echocardiography and risk for sudden
cardiac death assessment
Several factors are known to be indicators of a risk of sudden
death: a previous aborted cardiac arrest, one or more episodes of
non-sustained ventricular tachycardia, unexplained syncope,
and a history of sudden death in young family members (27-31).
Using 2D echocardiographic measurements Spirito et al showed
that the risk of sudden death increased progressively in direct
re-lation to wall thickness (P=0.001). The risk of sudden death was
less than 2.6 per 1000 person-years in those with a wall thickness
less than 19 mm, and went up to 18.2 per 1000 person-years (1.8%/
year) in those with a wall thickness of 30 mm or more (31) (Fig. 1).
Some patients deemed to be at increased risk for sudden cardiac
death because of massive thickening may be offered
prophylac-tic implantable cardioverter defibrillator (ICD) placement.
Treatment of symptoms
Treatment of HCM patients is guided by patient's symptoms
and echo findings. In patients with no or only mild symptoms the
approach of watchful waiting is often appropriate (19). Though
Figure 1. Relation between maximal left-ventricular-wall thickness and the risk of sudden death in 480 patients with hypertrophic cardiomyo-pathy. The incidence of sudden death increased progressively and in di-rect relation to maximal wall thickness (P=0.001 by the Chi-square test for trend) (31)
(Reproduced from Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000;342:1778-85 : Copyright © 2000 with permission of Massachusetts Medical Society).
patients with non-obstructive HCM are empirically offered
vera-pamil and beta blockade to improve symptoms, relief of ischemia
by limiting heart rate rise may be their main action.
Echocardiography is a valuable tool to understand the
pat-hophysiology of obstruction. Echocardiography data indicates
that systolic anterior motion (SAM) of the mitral valve is initiated
by flow drag; the mitral valve is swept toward the septum by the
pushing force of flow (Fig. 2). After mitral-septal contact,
obst-ruction begets further obstobst-ruction as the pressure gradient
pus-hes the mitral valve into the septum. The obstruction is best
described as: flow drag triggered, time dependent, amplifying
fe-edback loop (32-34) (Figures 3-5).
Two thirds of the symptomatic obstructed patients can be
successfully managed long term with medical treatment alone
without any other intervention (35). Drugs that are useful in
treat-ment of obstruction are the negative inotropes (
β-blockers,
vera-pamil, disopyramide). By reducing ejection acceleration of early
Figure 2. From the two-dimensional echocardiogram, four frames were identified: initial mitral leaflet coaptation, just before mitral-septal con-tact, mitral-septal contact and immediately after mitral-septal contact. The protruding mitral leaflet moves in an arc toward the septum until its tip contacts the septum. In the frame after contact, a portion of the body of the leaflet usually comes into apposition as well
(Reprinted from the Journal of the American College of Cardiology, Vol 22, number 3, Sherrid MV, Chu CK, Delia E, Mogtader A, Dwyer EM, Jr. An echocardiographic study of the fluid mec-hanics of obstruction in hypertrophic cardiomyopathy., Pages No. 816-25, Copyright (1993), with permission from the American College of Cardiology Foundation).
Coaptation Just Before Contact After Contact
Contact
Figure 3. Early in systole flow drag is the dominant hydrodynamic force on the mitral leaflet. After mitral-septal contact the pressure difference is the force that pushes the mitral leaflet further into the septum.
(Modified from references 32 and 33)
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Figure 5. Proposed explanation of pressure gradient development before and after treatment of obstruction. Before treatment (top tracing), rapid left ventricular acceleration apical of the mitral valve, shown as a hori-zontal thick arrow, triggers early systolic anterior motion (SAM) and early mitral-septal (M-S) contact. Once mitral-septal contact occurs, a narro-wed orifice develops, and a pressure difference results. The pressure dif-ference forces the leaflet against the septum, which decreases the orifi-ce size and further increases the pressure differenorifi-ce. An amplifying feed-back loop is established, shown as a rising spiral. The longer the leaflet is in contact with the septum, the higher the pressure gradient. After tre-atment (bottom tracing), negative inotropes slow early SAM (shown as a horizontal wavy arrow) and may thereby decrease the force on the mitral leaflet, delaying SAM. Mitral-septal contact would occur later, leaving less time in systole for the feedback loop to narrow the orifice. This wo-uld reduce the final pressure difference. Delaying SAM may also allow more time for papillary muscle shortening to provide countertraction. In the figure, for clarity, the "before" arrow is positioned above the "after" ar-row, although at the beginning of systole they both actually begin with a pressure gradient of 0 mm Hg
(Reproduced from Sherrid MV, Pearle G, Gunsburg DZ. Mechanism of benefit of negative inot-ropes in obstructive hypertrophic cardiomyopathy. Circulation 1998; Vol 97 No. 1: pages 41-7 Copyright (1998) with permission of LWW).
Figure 4. CW Doppler through jet is concave to the left, “dagger shaped” due to amplifying feedback loop exponentially increasing the obstruction
flow, the early systolic pushing force on the protruding mitral
le-aflets is reduced, thus delaying the SAM and mitral-septal
con-tact (33) (Fig. 6).
Finding the right medication and the right dosage for
symptomatic patients can be challenging for the treating
physi-cian. The first step in medical treatment is stopping medications
that may worsen obstruction: angiotensin converting enzyme
in-hibitors, angiotensin receptor blockers, nifedipine, amlodipine,
long and short acting nitrates and
β-blockers (36). The first
me-dication to be tried in symptomatic patients are
β-blockers.
Af-ter IV or oral
β-blocker administration, Doppler gradient is
chec-ked. If good response is achieved, with reduction of the gradient
to less than 30 mmHg,
β-blockers are used as single therapy
with a goal of resting heart rate between 55 and 60 bpm.
Additi-on of disopyramide, or verapamil substitutiAdditi-on is cAdditi-onsidered if
symptoms persist and gradient remains more than 30 mmHg
(36). At our institution the preference is to add disopyramide to
β-blockers for a synergistic effect. Repeat echo is done 2.5
ho-urs after a single dose of 250 mg disopyramide, or 2 days after
disopyramide controlled release (CR) 250 mg every 12 hours, has
begun to assess acute response. Patients who respond to
di-sopyramide with a gradient less than 30 mm Hg are continued
on the combination. Amiodarone or any other antiarrhythmic
drug are stopped when disopyramide is begun. In patients with
contraindication to disopyramide, oral verapamil is begun at
240-360 mg/day in divided doses. When the gradient remains
greater than 30 mmHg and patients are still symptomatic
despi-te medication manipulation, Doppler examinations of left
ventri-cular acceleration may help the clinician to decide further
ma-nagement (Fig. 6). If left ventricular acceleration is not
signifi-cantly slowed by medical treatment, or if heart rate has not
slo-wed, then the medication can be increased. If acceleration in
the left ventricle has slowed but there is still significant
obstruc-tion, medication alone may not be adequate to eliminate
obst-ruction because of adverse anatomy and further
non-pharma-cologic interventions are required (36, 37) (Fig. 7).
Echocardiography is extremely helpful for close monitoring
of intravenous
β-blocker treatment of critically ill HCM patients
with severe acute obstruction and congestive heart failure,
whe-re parameters can be followed in whe-real time. The best
pharmaco-logic combination for patients in shock due to obstruction is
phenylephrine for pressure support and
β-blockers for decrease
in gradient (33,36). Dobutamine or dopamine or epinephrine
sho-uld be avoided as they usually will worsen precarious situations.
Echocardiography role in surgical
septal myectomy
Obstructed patients who fail medical therapy, defined as
lack of gradient reduction below 50 mmHg and persistent
disab-ling symptoms, are usually offered invasive treatment: surgical
septal myectomy, alcohol septal ablation, or DDD pacemaker.
Surgical septal myectomy is the gold standard for obstructed
pa-tients refractory to treatment. It results in immediate relief of
obstruction and improvement of mitral regurgitation. In
speciali-zed centers operative mortality is 1% and the rate of surgical
success > 95% in those without comorbid cardiac or medical
conditions. Postoperative resting gradients are abolished and
parallel improvement in symptoms are achieved (5, 38-45).
Figure 6. Comparison of left ventricular pulsed Doppler tracings, before treatment (left panel) and after successful medical treatment (right panel). The sample volume was 2.5 cm apical of mitral valve coaptation point. Before treatment, ejection acceleration was rapid (arrowhead) and velocity peaked in the first half of systolic. After treatment, ejection accel-eration was slowed (arrowhead) and velocity peaked in the second half of a systole. Systolic anterior mitral motion was delayed and a 96 mm Hg gradient was eliminated. Note, that though acceleration slowed, peak velocity remained virtually unchanged. This contrast highlights the impor-tance of acceleration and the timing of ejection in successful medical therapy. The velocity calibration is identical in both panels. The scale is 20 cm/sec between white marks
(Reproduced from Sherrid MV, Pearle G, Gunsburg DZ. Mechanism of benefit of negative inotropes in obstructive hypertrophic cardiomyopathy. Circulation 1998; Vol 97 No. 1: pages 41-7 Copyright (1998) with permission of LWW).
Figure 7. Proposed algorithm for medical therapy of symptomatic hypertrophic cardiomyopathy
Patients are considered for medical therapy of obstruction if they have a gradient greater than 30 mmHg at rest or after provocation with Valsalva maneuver or exercise. The criterion of 30 mmHg may prompt medical the-rapy; surgical or ablation interventions is usually reserved for patients who fail medical therapy but have gradients at rest or after provocation greater than 50 mmHg. Either disopyramide or verapamil may be selected as the second-line agent. Disopyramide is added to ββ-blockade, while verapamil is generally substituted for ββ-blockade
(Adapted from reference 36)
Symptomatic HCM
Improved
Non-obstructed
Symptoms Persist Symptoms + Gradient Persist Symptoms persist or drug intolerance Symptoms persist or drug tolerance Symptoms persist or drug intolerance Obstructed* Improved Improved Improved Improved Verapamil B-blockade Substitute B-blockade Substitute Verapamil Substitute Disopyramide + B-blockade Add Disopyramide
Surgical intervention to relieve obstruction in HCM is
techni-cally challenging because in HCM multiple anatomical factors
may play a role in gradient development and symptomatology.
Key factors leading to SAM with mitral-septal contact are:
1. prominent septal bulge which directs the blood flow
be-hind mitral valve coaptation (5, 32, 34),
2. large, slack mitral valve and anteriorly positioned
coapta-tion plane (5, 10, 46-48),
3. anterior position and agglutination of the papillary muscles
to the anterior left ventricular wall contributing to anterior
positi-on of coaptatipositi-on plane (5, 49).
The surgeon may need to address all three anatomical
ab-normalities, which lead to a very crowded base of left ventricle
and crucial overlap between the inflow and outflow portions of
the left ventricle (5). McCully et al suggested, in a series of 47
pa-tients who underwent septal myectomy alone, that asymmetric
hypertrophy, severe systolic anterior motion of the mitral
leaf-let(s) on preoperative echocardiography can identify patients
who are most likely to benefit from septal myectomy (50).
Technical difficulties are due especially to a very small and
deep operative field offered by the aortotomy and small left
vent-ricle chamber dimensions. Visualization is accessible only to the
principal surgeon, and the anatomy of the empty heart can be
ambiguous, leading to imprecision in the extent of myectomy that
may result in either an inadequate small resection with
persis-tent obstruction (51), or too large, and a ventricular septal defect
(0% to 2%), or complete heart block (5, 38-45).
Preoperative TTE is a necessary guide for the surgeon in
planning the operation. It gives the surgeon precise
measure-ments on septum thickness and how deep he needs to go into
the left ventricle to excise the midseptal bulge, as well as to
eva-luate the length and floppiness of the mitral valve leaflets,
papil-lary muscle abnormalities and/or anomalous insertion (better
evaluated by TEE). If the TTE imaging is inadequate
transesopha-geal echocardiography (TEE) is required. Important information
is also provided by the TEE pre-bypass, as real-time
measure-ments and assessment of the whole picture are evident. New
un-suspected findings (patent foramen ovale, mitral valve prolapse
and flail mitral valve leaflet, abnormal papillary muscles, etc)
ha-ve been reported by Ommen et al in 17% of 256 patients
under-going septal myectomy. These findings resulted in an alteration
of the surgical plan for 9% of the patients (5, 52, 53).
Persistent SAM, resting outflow gradient more than 30 mm Hg
or more than 50 mmHg with provocation (intravenous inotropic
agents or post-PVC), moderate to severe mitral regurgitation are
indications for placing the patient back on heart-lung bypass for
revision (5, 18, 54). Using these criteria 7 - 20% of the patients
we-re found to need we-revision: either additional we-resection, or further
mitral valve repair (5, 53, 54). In successful cases of extended
sep-tal myectomy, mitral valvuloplasty and papillary muscle release
(Fig. 8.), as seen in a R-P-R (resection - plication - release)
opera-tion described by Swistel (55), the post-surgical study will show: 1)
a dramatic thinning of the septum, with widening of the left
ventri-cular outflow tract to a width similar to that in the normal subjects,
2) resolution of systolic anterior motion and the left ventricular
outflow tract gradient, 3) marked reduction or abolition of mitral
regurgitation, 4) decreased anterior mitral leaflet length
and 5) more posterior mitral leaflet coaptation point (5, 53, 55).
Late recurrent obstruction can be rarely encountered.
Minaka-ta et al reported 13 patients needing repeat myectomy in a series
of 610 patients after classic myectomy operations, which included
7 patients from outside institutions. Mechanisms included too
limi-ted myectomy at the initial operation, mid-ventricular obstruction,
unrecognized anomalies of papillary muscles, and ventricular
re-modeling (especially in pediatric patients) (56). Repeat myectomy
can be performed with excellent outcomes. Need for re-operation
may be reduced with current surgical approaches that include a
more extended resection of the mid-ventricular septum, relief of
papillary muscle anomalies, mitral valve plication, and routine use
of intraoperative transesophageal echocardiography (5, 56).
Figure 8. Surgical separation of ventricular inflow from outflow in obst-ructive hypertrophic cardiomyopathy, and extended myectomy and papil-lary muscle mobilization. (A) Illustration of outflow relative to the mitral valve in early systole. Note the anterior position of the mitral valve coap-tation. The prominent midseptal bulge redirects outflow so that it comes from a relatively posterior direction, catching the anteriorly positioned mitral valve and pushing it into the septum. (B) After subaortic septal re-section. The subaortic septum has been resected, but only down to the tips of the mitral leaflets. Flow is still redirected by the remaining septal bulge so that it comes from a posterior direction. It still catches the mitral valve; systolic anterior motion persists, as does the obstruction. (C) The septal bulge below the mitral leaflet tips has been resected, an extended myectomy. Now, flow tracks more anteriorly and medially, away from the mitral leaflets. (D) Mobilization and partial excision of the papillary musc-les is added to extended myectomy. The mitral coaptation plane is now more posterior, explicitly out of the flow stream
(Reprinted from the Annals of Thoracic Surgery, Vol 75, number 2, Sherrid MV, Chaudhry FA, Swistel DG. Obstructive hypertrophic cardiomyopathy: echocardiography, pathophysiology, and the continuing evolution of surgery for obstruction, Pages No. 620-32, Copyright (2003), with permission from the Elsevier)
A
B
C
Echocardiography in DDD pacemaker
treatment of HCM
Historically the next intervention that was applied to reduce
LVOT obstruction was DDD pacing with atrioventricular (AV)
de-lay (57-59). Though pacing cannot be considered a primary
stra-tegy to treat obstruction it appears useful in certain patients. The
mechanism of the therapeutic effect derived from pacing is
unc-lear. It is proposed that the initiation of the electrical impulse in
the apex of the right ventricle alters the LV systolic contraction
sequence leading to a reduction in the outflow gradient (57).
Ec-hocardiography has been an important technique in the
evaluati-on and follow-up of respevaluati-onse to this interventievaluati-on. Fananapazir in
a study of 44 patients with obstructive HCM showed that
implan-tation of a DDD pacemaker improved symptoms and was
asso-ciated with significant reduction in LVOT gradient (59). M-mode
in the parasternal long axis and Doppler measurements
(continu-ous or pulsed wave) of the LVOT in apical 3 or 5 chamber views
were used to demonstrate the response to pacing with
reducti-on in SAM and LVOT velocity. The respreducti-onse was simultaneous
with the start of atrioventricular pacing (59) (Fig. 9). Doppler
con-siderations may aid selecting optimal AV delay (60).
Initial observational findings of relief of symptoms, reduction
of the gradient and LV remodeling (61, 62) have not been
reprodu-ced in randomized clinical trials (63, 64). These showed a large
placebo effect and no significant improvement in objective
me-asures of exercise capacity, and incomplete gradient reduction
(30 to 50 mm Hg average residual gradient after pacing) (63, 64).
Failure to relieve symptoms is common, with fewer than 40 % of
patients still having improved symptoms at five years follow-up
(57, 65). Also pacing may be detrimental to diastolic function (60).
Two particular groups of population had been shown to
ha-ve a good long term clinical response to DDD pacemaker: elderly
patients ≥ 65 years of age (64), and patients with normal septal
curvature and preserved elliptical LV cavity shape (66). Knowing
that degree of improvement is less than that achieved with the
other therapies dual-chamber pacing should be limited to elderly
patients (≥ 70 years of age), those with significant co morbidities
preventing them from having other therapies, those who require
pacing for bradycardia, or who receive devices for sudden death
prevention (37).
Role of echocardiography in alcohol septal ablation
For patients with refractory symptoms and high gradients on
medication and not suitable for surgery because of comorbidities,
percutaneous septal reduction via alcohol septal ablation (ASA)
is an alternative therapy for relief of obstruction and improvement
of symptoms. Absolute ethanol is infused into a septal branch of
the left anterior descending coronary artery (LAD) to specifically
induce necrosis of the hypertrophied septum (67). The technique
has a periprocedural mortality of 1-2%, lower in experienced
cen-ters (68-70). Hypertrophic cardiomyopathy experts in the United
States have expressed reservation about alcohol septal ablation
because procedural complications occur at least as frequently as
in surgical septal myectomy and long term results have not been
yet been reported.
Alcohol septal ablation is a viable alternative to surgery in
patients considered as high risk for surgery. Irreversible
comple-te heart block requiring permanent pacemaker implantation
oc-curs in 7-18% of the patients (68, 71). Also of concern is the scar
that can be a substrate for late increased risk of ventricular
arrhythmias. Alcohol septal ablation should therefore not be
do-ne in young patients < 40 years.
Echocardiography is a valuable tool to choose the site of
abla-tion, as well as for evaluation of results. Myocardial contrast
echo-cardiography (MCE) guides the targeted delivery of ethanol during
ASA: there is a relation between the MCE risk area and infarct
si-ze determined by enzymatic and radionuclide methods (72,73). This
technique to guide ASA was implemented in late 1990's in Europe
by Faber and Seggewiss and in the US by Lakkis and Nagueh.
Lak-kis et al described their technique in 33 patients (72). After
comple-tion of initial angiography a balloon catheter is introduced into the
first large septal perforator and inflated. With the balloon inflated
echocardiography contrast is injected through the balloon lumen
to delineate the area supplied by the septal branch, to assure that
contrast does not go to the LV apex or lateral wall, papillary
musc-les, RV free wall or any other place not wanted (72) (Figures 10, 11).
In the US dilute Definity is used; in Europe Levovist.
Intra-procedu-ral MCE guidance leads to a changes in interventional strategy in
15-20% patients; in 7-11% bubbles are seen distant from the
expec-ted septal target region is detecexpec-ted, leading to a target vessel
change (68, 74). In 5-7% the procedure is aborted due
inappropri-ate target vessel and patients are referred for surgery (68).
Figure 9. M-mode echocardiogram and continuous-wave Dopplerrecor-dings obtained during sinus rhythm and immediately after initiation of atrial synchronized ventricular pacing mode from a 24-year-old patient with obst-ructive hypertrophic cardiomyopathy. Top panel shows the M-mode echo-cardiographic tracing recorded at a paper speed of 50 mm/sec. At baseline, there is marked systolic anterior motion of the mitral valve with prolonged mitral-septal apposition (A); after initiation of dual-chamber (DDD) pacing, the magnitude of mitral systolic motion is significantly reduced with disap-pearance of the mitral-septal contact (B). Pacing is also associated with subtle paradoxical movement of the interventricular septum (VS). Bottom pa-nel shows continuous-wave Doppler interrogation of left ventricular outflow tract velocities obtained at the same study and in the same patient and re-corded at paper speed of 25 mm/sec. At baseline, peak velocity is 4.2 m/sec (C), corresponding to an estimated gradient of 70 mm Hg; with DDD pacing, peak velocity is reduced to 2.2 m/sec (D) (estimated gradient, 20 mm Hg) PW- posterior left ventricular free wall, RV- right ventricle
(Reproduced from Fananapazir L, Cannon RO, 3rd, Tripodi D, Panza JA. Impact of dual-chamber permanent pacing in patients with obstructive hypertrophic cardiomyopathy with symptoms ref-ractory to verapamil and beta-adrenergic blocker therapy. Circulation 1992; Vol 85, No. 6: pages 2149-61 Copyright (1992) with permission of LWW).
C
Depending on the septal artery size and the septal thickness,
1-3 mL of absolute ethanol is slowly instilled through the lumen of
the inflated balloon catheter and left in place for 5 minutes. After
balloon deflation and removal, angiography is performed to
con-firm the patency of the LAD and the occlusion of the target
sep-tal branch. Some groups will inject other sepsep-tal branches during
the same sitting if deemed necessary (72). Introduction of MCE
as guidance in choosing the accurate septal branch was
associ-ated with a more targeted alcohol injection and a higher
percen-tage of short (92% vs. 70%) (75), mid term (88%) (76) and 1 year
success rate (99%) (69). In patients treated before the
introduc-tion of intraprocedural myocardial contrast echocardiography
the main reason for unsatisfactory gradient reduction was
su-boptimal scar placement (74, 77).
Echocardiography offers insights into the mechanisms of
be-nefit of ASA. It induces an acute decrease in septal thickening
and decrease in acceleration of LV ejection (73). This translates
into decrease in drag forces. Also, electromechanical changes
after ASA with the development of bundle branch block (right
bundle branch block alone in 60% and with left anterior
hemib-lock in 20%) lead to further inhomogeneity in LV contraction (78).
There are no acute geometric changes, no immediate effect on
the mitral valve apparatus (79).
On the follow up echocardiography basal septal thickness
decreases significantly, with decreased systolic excursion.
Dec-reased acceleration persists acting in synergy with the
decre-ased septal thickness (72, 79). The angle between ventricular
flow and mitral valve leaflets decreases. Mitral regurgitation
improvement parallels the improvement in LVOT obstruction.
Af-ter six weeks, LVOT diameAf-ter and the distance between anAf-terior
mitral leaflet and the septum were greater in comparison to
ba-seline. Further benefits beyond the acute response from ASA
can be explained by LV remodeling (69).
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LA- left atrium, LV- left ventricle, PW- posterior wall, RV- right ventricle, SW- septal wall (Reproduced from Lakkis NM, Nagueh SF, Kleiman NS, Killip D, He ZX, Verani MS, et al. Echo-cardiography-guided ethanol septal reduction for hypertrophic obstructive cardiomyopathy. Circulation 1998; Vol 98, No. 17: pages 1750-5, Copyright (1998) with permission of LWW). Figure 10. Apical 4-chamber view showing hypertrophied septum before (left) and after (right) contrast injection into target septal branch deline-ating area to be infarcted
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